HU196972B - Process for producing new quinazoline derivatives and pharmaceutical compositions containing them as active components - Google Patents
Process for producing new quinazoline derivatives and pharmaceutical compositions containing them as active components Download PDFInfo
- Publication number
- HU196972B HU196972B HU864192A HU419286A HU196972B HU 196972 B HU196972 B HU 196972B HU 864192 A HU864192 A HU 864192A HU 419286 A HU419286 A HU 419286A HU 196972 B HU196972 B HU 196972B
- Authority
- HU
- Hungary
- Prior art keywords
- nujol
- tetrahydro
- formula
- ethyl
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 48
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title claims 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 136
- 150000003839 salts Chemical class 0.000 claims abstract description 70
- 150000002367 halogens Chemical class 0.000 claims abstract description 14
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 13
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 5
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
- 239000001301 oxygen Substances 0.000 claims abstract description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 3
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims abstract description 3
- 239000003937 drug carrier Substances 0.000 claims abstract 2
- -1 3- (4-bromo-2-fluorobenzyl) -7-chloro-1,2,3,4-tetrahydro-2,4-dioxoquinazolin-1-yl Chemical group 0.000 claims description 135
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 97
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 239000004480 active ingredient Substances 0.000 claims description 8
- 150000001447 alkali salts Chemical class 0.000 claims description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 239000007858 starting material Substances 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 2
- 229910052717 sulfur Inorganic materials 0.000 abstract description 2
- 125000004434 sulfur atom Chemical group 0.000 abstract description 2
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 216
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 136
- 238000006243 chemical reaction Methods 0.000 description 62
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- 239000000203 mixture Substances 0.000 description 56
- 238000002844 melting Methods 0.000 description 53
- 230000008018 melting Effects 0.000 description 53
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
- 239000002904 solvent Substances 0.000 description 40
- 235000011054 acetic acid Nutrition 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 21
- 239000002253 acid Substances 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
- 241000700159 Rattus Species 0.000 description 10
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 description 9
- 230000002411 adverse Effects 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 150000003246 quinazolines Chemical class 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 8
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 206010012601 diabetes mellitus Diseases 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 150000007529 inorganic bases Chemical class 0.000 description 6
- 239000011630 iodine Substances 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 210000003497 sciatic nerve Anatomy 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 239000000600 sorbitol Substances 0.000 description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 5
- 229910052742 iron Inorganic materials 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000002480 mineral oil Substances 0.000 description 5
- 235000010446 mineral oil Nutrition 0.000 description 5
- 150000007530 organic bases Chemical class 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- FQXIRXTVFVCJFQ-UHFFFAOYSA-N ethyl 2-[3-[(4-bromo-2-fluorophenyl)methyl]-7-chloro-2,4-dioxoquinazolin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F FQXIRXTVFVCJFQ-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
- BKDOBPYOBVPQNV-UHFFFAOYSA-N 2-[3-[(3,4-dichlorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC=C(Cl)C(Cl)=C1 BKDOBPYOBVPQNV-UHFFFAOYSA-N 0.000 description 3
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 3
- ILXCEJVHWNYEFQ-UHFFFAOYSA-N 3-[(4-bromo-2-fluorophenyl)methyl]-7-chloro-1h-quinazoline-2,4-dione Chemical compound FC1=CC(Br)=CC=C1CN1C(=O)C2=CC=C(Cl)C=C2NC1=O ILXCEJVHWNYEFQ-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- YTXVFFFUJLKZPJ-UHFFFAOYSA-N ethyl 2-(2-carbamoyl-5-chloroanilino)acetate Chemical compound CCOC(=O)CNC1=CC(Cl)=CC=C1C(N)=O YTXVFFFUJLKZPJ-UHFFFAOYSA-N 0.000 description 3
- JMGYCAMULWQVAM-UHFFFAOYSA-N ethyl 2-[3-[(4-chlorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C2=CC=CC=C2C(=O)N1CC1=CC=C(Cl)C=C1 JMGYCAMULWQVAM-UHFFFAOYSA-N 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- SXONDGSPUVNZLO-UHFFFAOYSA-N zenarestat Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F SXONDGSPUVNZLO-UHFFFAOYSA-N 0.000 description 3
- RLTFBWCBGIZCDQ-UHFFFAOYSA-N (4-bromo-2-fluorophenyl)methanamine Chemical compound NCC1=CC=C(Br)C=C1F RLTFBWCBGIZCDQ-UHFFFAOYSA-N 0.000 description 2
- BIULOUDIFIMWIS-UHFFFAOYSA-N 2-(3-benzyl-2,4-dioxoquinazolin-1-yl)acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC=CC=C1 BIULOUDIFIMWIS-UHFFFAOYSA-N 0.000 description 2
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical compound NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 2
- CUMHLVTXUSTXCL-UHFFFAOYSA-N 2-[2,4-dioxo-3-(pyridin-2-ylmethyl)quinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC=CC=N1 CUMHLVTXUSTXCL-UHFFFAOYSA-N 0.000 description 2
- KMFPQQKQTZIHOD-UHFFFAOYSA-N 2-[2,4-dioxo-3-(thiophen-2-ylmethyl)quinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC=CS1 KMFPQQKQTZIHOD-UHFFFAOYSA-N 0.000 description 2
- RTDAUOSYMUJVMN-UHFFFAOYSA-N 2-[3-(naphthalen-1-ylmethyl)-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound C1=CC=C2C(CN3C(=O)C4=CC=CC=C4N(C3=O)CC(=O)O)=CC=CC2=C1 RTDAUOSYMUJVMN-UHFFFAOYSA-N 0.000 description 2
- SEOOOAKCIOZNBC-UHFFFAOYSA-N 2-[3-(naphthalen-2-ylmethyl)-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound C1=CC=CC2=CC(CN3C(=O)C4=CC=CC=C4N(C3=O)CC(=O)O)=CC=C21 SEOOOAKCIOZNBC-UHFFFAOYSA-N 0.000 description 2
- CGUJPDPCPMHNOI-UHFFFAOYSA-N 2-[3-[(2,3-dichlorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC=CC(Cl)=C1Cl CGUJPDPCPMHNOI-UHFFFAOYSA-N 0.000 description 2
- DNTSYFXIUZDXFS-UHFFFAOYSA-N 2-[3-[(2,4-dichlorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC=C(Cl)C=C1Cl DNTSYFXIUZDXFS-UHFFFAOYSA-N 0.000 description 2
- UVRJJIDHOSRAST-UHFFFAOYSA-N 2-[3-[(2,6-dichlorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=C(Cl)C=CC=C1Cl UVRJJIDHOSRAST-UHFFFAOYSA-N 0.000 description 2
- IKFJOWZPNLODOF-UHFFFAOYSA-N 2-[3-[(3,4-dichlorophenyl)methyl]-2,4-bis(sulfanylidene)quinazolin-1-yl]acetic acid Chemical compound S=C1N(CC(=O)O)C2=CC=CC=C2C(=S)N1CC1=CC=C(Cl)C(Cl)=C1 IKFJOWZPNLODOF-UHFFFAOYSA-N 0.000 description 2
- SMZPIUPUPYXXLZ-UHFFFAOYSA-N 2-[3-[(3,4-dichlorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]propanoic acid Chemical compound O=C1N(C(C(O)=O)C)C2=CC=CC=C2C(=O)N1CC1=CC=C(Cl)C(Cl)=C1 SMZPIUPUPYXXLZ-UHFFFAOYSA-N 0.000 description 2
- FBKRMYUIJMDCAD-UHFFFAOYSA-N 2-[3-[(3,4-dichlorophenyl)methyl]-4-oxo-2-sulfanylidenequinazolin-1-yl]acetic acid Chemical compound S=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC=C(Cl)C(Cl)=C1 FBKRMYUIJMDCAD-UHFFFAOYSA-N 0.000 description 2
- VFWLWNUNOROOEK-UHFFFAOYSA-N 2-[3-[(3,5-dichlorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC(Cl)=CC(Cl)=C1 VFWLWNUNOROOEK-UHFFFAOYSA-N 0.000 description 2
- UMCXSJDMPLOOOZ-UHFFFAOYSA-N 2-[3-[(4-bromo-2-fluorophenyl)methyl]-2,4-dioxo-7-(trifluoromethyl)quinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(C(F)(F)F)=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F UMCXSJDMPLOOOZ-UHFFFAOYSA-N 0.000 description 2
- QWCDEEFYNYRJCB-UHFFFAOYSA-N 2-[3-[(4-bromo-2-fluorophenyl)methyl]-5,7-dichloro-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC(Cl)=C2C(=O)N1CC1=CC=C(Br)C=C1F QWCDEEFYNYRJCB-UHFFFAOYSA-N 0.000 description 2
- RGDBMMUKMLRWFI-UHFFFAOYSA-N 2-[3-[(4-bromo-2-fluorophenyl)methyl]-6-methoxy-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1C2=CC(OC)=CC=C2N(CC(O)=O)C(=O)N1CC1=CC=C(Br)C=C1F RGDBMMUKMLRWFI-UHFFFAOYSA-N 0.000 description 2
- OIYOSPDHASNIID-UHFFFAOYSA-N 2-[3-[(4-chlorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC=C(Cl)C=C1 OIYOSPDHASNIID-UHFFFAOYSA-N 0.000 description 2
- CNGDNKAFSFRBAU-UHFFFAOYSA-N 2-[3-[(4-methoxyphenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC=CC=C2N(CC(O)=O)C1=O CNGDNKAFSFRBAU-UHFFFAOYSA-N 0.000 description 2
- XDDPSWFBHOGNLC-UHFFFAOYSA-N 2-[3-[(4-methylphenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound C1=CC(C)=CC=C1CN1C(=O)C2=CC=CC=C2N(CC(O)=O)C1=O XDDPSWFBHOGNLC-UHFFFAOYSA-N 0.000 description 2
- XPKRKIMKOLPWQI-UHFFFAOYSA-N 2-[6,7-dichloro-3-[(2-fluoro-4-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=C(Cl)C=C2C(=O)N1CC1=CC=C(I)C=C1F XPKRKIMKOLPWQI-UHFFFAOYSA-N 0.000 description 2
- FQUMHBXENNAXTG-UHFFFAOYSA-N 2-[7-bromo-3-[(4-bromo-2-fluorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Br)=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F FQUMHBXENNAXTG-UHFFFAOYSA-N 0.000 description 2
- QKTDABZFNMEKGF-UHFFFAOYSA-N 2-[7-chloro-3-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(Cl)C(C(F)(F)F)=C1 QKTDABZFNMEKGF-UHFFFAOYSA-N 0.000 description 2
- LZIYHKUKOLSJIE-UHFFFAOYSA-N 2-[7-fluoro-3-[(2-fluoro-4-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(F)=CC=C2C(=O)N1CC1=CC=C(I)C=C1F LZIYHKUKOLSJIE-UHFFFAOYSA-N 0.000 description 2
- DRXBYUWCDFAXPM-UHFFFAOYSA-N 2-amino-4-bromo-n-[(4-bromo-2-fluorophenyl)methyl]benzamide Chemical compound NC1=CC(Br)=CC=C1C(=O)NCC1=CC=C(Br)C=C1F DRXBYUWCDFAXPM-UHFFFAOYSA-N 0.000 description 2
- FYWKGLNCJDQKBK-UHFFFAOYSA-N 2-amino-n-[(3,4-dichlorophenyl)methyl]benzamide Chemical compound NC1=CC=CC=C1C(=O)NCC1=CC=C(Cl)C(Cl)=C1 FYWKGLNCJDQKBK-UHFFFAOYSA-N 0.000 description 2
- PSPZHJCIFHRWNP-UHFFFAOYSA-N 3-benzyl-2-sulfanylidene-1h-quinazolin-4-one Chemical compound S=C1NC2=CC=CC=C2C(=O)N1CC1=CC=CC=C1 PSPZHJCIFHRWNP-UHFFFAOYSA-N 0.000 description 2
- XMHNLZXYPAULDF-UHFFFAOYSA-N 4-bromo-1-(bromomethyl)-2-fluorobenzene Chemical compound FC1=CC(Br)=CC=C1CBr XMHNLZXYPAULDF-UHFFFAOYSA-N 0.000 description 2
- VGIAGYCJTSPJBK-UHFFFAOYSA-N 7-bromo-3-[(2-fluoro-4-iodophenyl)methyl]-1h-quinazoline-2,4-dione Chemical compound FC1=CC(I)=CC=C1CN1C(=O)C2=CC=C(Br)C=C2NC1=O VGIAGYCJTSPJBK-UHFFFAOYSA-N 0.000 description 2
- UGXLFKMTWACGHL-UHFFFAOYSA-N 7-bromo-3-[(4-bromo-2-fluorophenyl)methyl]-1h-quinazoline-2,4-dione Chemical compound FC1=CC(Br)=CC=C1CN1C(=O)C2=CC=C(Br)C=C2NC1=O UGXLFKMTWACGHL-UHFFFAOYSA-N 0.000 description 2
- QRUPDIJQZCABTC-UHFFFAOYSA-N 7-chloro-1h-3,1-benzoxazine-2,4-dione Chemical compound N1C(=O)OC(=O)C=2C1=CC(Cl)=CC=2 QRUPDIJQZCABTC-UHFFFAOYSA-N 0.000 description 2
- 102000016912 Aldehyde Reductase Human genes 0.000 description 2
- 108010053754 Aldehyde reductase Proteins 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 206010029333 Neurosis Diseases 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- BLRWRUUEWGAHSI-UHFFFAOYSA-N OC1=NC(NC2=CC=CC=C12)=O.[I] Chemical compound OC1=NC(NC2=CC=CC=C12)=O.[I] BLRWRUUEWGAHSI-UHFFFAOYSA-N 0.000 description 2
- 102000004316 Oxidoreductases Human genes 0.000 description 2
- 108090000854 Oxidoreductases Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 2
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- UXTDCASLMNAHJM-UHFFFAOYSA-N ethyl 2-(2-carbamoylanilino)acetate Chemical compound CCOC(=O)CNC1=CC=CC=C1C(N)=O UXTDCASLMNAHJM-UHFFFAOYSA-N 0.000 description 2
- XBMXCCVWDVVEJU-UHFFFAOYSA-N ethyl 2-(6,7-dichloro-2,4-dioxoquinazolin-1-yl)acetate Chemical compound ClC1=C(Cl)C=C2C(=O)NC(=O)N(CC(=O)OCC)C2=C1 XBMXCCVWDVVEJU-UHFFFAOYSA-N 0.000 description 2
- UPFJFNADBNXIKQ-UHFFFAOYSA-N ethyl 2-[6,7-dichloro-3-[(2-fluoro-4-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C2=CC(Cl)=C(Cl)C=C2C(=O)N1CC1=CC=C(I)C=C1F UPFJFNADBNXIKQ-UHFFFAOYSA-N 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- KNDSECWRJDKHLW-UHFFFAOYSA-N n-[(3,4-dichlorophenyl)methyl]-2-nitrobenzenesulfonamide Chemical compound [O-][N+](=O)C1=CC=CC=C1S(=O)(=O)NCC1=CC=C(Cl)C(Cl)=C1 KNDSECWRJDKHLW-UHFFFAOYSA-N 0.000 description 2
- VXSPYZNLEXUXOC-UHFFFAOYSA-N n-[(4-bromo-2-fluorophenyl)methyl]-4-fluoro-2-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC(F)=CC=C1C(=O)NCC1=CC=C(Br)C=C1F VXSPYZNLEXUXOC-UHFFFAOYSA-N 0.000 description 2
- 208000015238 neurotic disease Diseases 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- SSUDQIXBUJCZPX-UHFFFAOYSA-M sodium;2-[3-[(4-bromo-2-fluorophenyl)methyl]-7-chloro-2,4-dioxoquinazolin-1-yl]acetate Chemical compound [Na+].O=C1N(CC(=O)[O-])C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F SSUDQIXBUJCZPX-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 2
- 229960001052 streptozocin Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- QXQDNFBNUIJQQX-UHFFFAOYSA-N (2-fluoro-4-iodophenyl)methanamine Chemical compound NCC1=CC=C(I)C=C1F QXQDNFBNUIJQQX-UHFFFAOYSA-N 0.000 description 1
- IXHNFOOSLAWRBQ-UHFFFAOYSA-N (3,4-dichlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C(Cl)=C1 IXHNFOOSLAWRBQ-UHFFFAOYSA-N 0.000 description 1
- JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- TXJUTRJFNRYTHH-UHFFFAOYSA-N 1h-3,1-benzoxazine-2,4-dione Chemical compound C1=CC=C2C(=O)OC(=O)NC2=C1 TXJUTRJFNRYTHH-UHFFFAOYSA-N 0.000 description 1
- SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 description 1
- LMGCRCCMYRUJMT-UHFFFAOYSA-N 2-[(3,4-dichlorophenyl)methyl]-1,1-dioxo-4h-1$l^{6},2,4-benzothiadiazin-3-one Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1S(=O)(=O)C2=CC=CC=C2NC1=O LMGCRCCMYRUJMT-UHFFFAOYSA-N 0.000 description 1
- IRJWVIIDKZJNND-UHFFFAOYSA-N 2-[3-(3,4-dichlorophenyl)-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1C1=CC=C(Cl)C(Cl)=C1 IRJWVIIDKZJNND-UHFFFAOYSA-N 0.000 description 1
- VJZYICWSVPSCAD-UHFFFAOYSA-N 2-[3-[(2,5-dichlorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC(Cl)=CC=C1Cl VJZYICWSVPSCAD-UHFFFAOYSA-N 0.000 description 1
- GBMBFYYGBBVEGT-UHFFFAOYSA-N 2-[3-[(2-fluoro-4-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC=C(I)C=C1F GBMBFYYGBBVEGT-UHFFFAOYSA-N 0.000 description 1
- NHKMOIQOEIDYQP-UHFFFAOYSA-N 2-[3-[(3,4-dichlorophenyl)methyl]-2-oxo-4-sulfanylidenequinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=S)N1CC1=CC=C(Cl)C(Cl)=C1 NHKMOIQOEIDYQP-UHFFFAOYSA-N 0.000 description 1
- CQQITEUCHFMHBS-UHFFFAOYSA-N 2-[3-[(4-bromo-2-fluorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F CQQITEUCHFMHBS-UHFFFAOYSA-N 0.000 description 1
- SXEPCMGMVAWKLM-UHFFFAOYSA-N 2-[3-[(4-bromo-2-fluorophenyl)methyl]-7-methoxy-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound C=1C(OC)=CC=C(C2=O)C=1N(CC(O)=O)C(=O)N2CC1=CC=C(Br)C=C1F SXEPCMGMVAWKLM-UHFFFAOYSA-N 0.000 description 1
- DFZPFLMGYYCKPR-UHFFFAOYSA-N 2-[3-[(4-bromo-3-chlorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2C(=O)N1CC1=CC=C(Br)C(Cl)=C1 DFZPFLMGYYCKPR-UHFFFAOYSA-N 0.000 description 1
- PNPFUBVLCBECTD-UHFFFAOYSA-N 2-[3-[[3,5-bis(trifluoromethyl)phenyl]methyl]-7-chloro-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 PNPFUBVLCBECTD-UHFFFAOYSA-N 0.000 description 1
- YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
- NBGNXIJZQWDTEZ-UHFFFAOYSA-N 2-[7-bromo-3-[(2-fluoro-4-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Br)=CC=C2C(=O)N1CC1=CC=C(I)C=C1F NBGNXIJZQWDTEZ-UHFFFAOYSA-N 0.000 description 1
- MVKAITNDCSRXGD-UHFFFAOYSA-N 2-[7-chloro-3-[(2-fluoro-3-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=CC(I)=C1F MVKAITNDCSRXGD-UHFFFAOYSA-N 0.000 description 1
- GANUQUHEMPMSDL-UHFFFAOYSA-N 2-[7-chloro-3-[(3-chloro-4-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(I)C(Cl)=C1 GANUQUHEMPMSDL-UHFFFAOYSA-N 0.000 description 1
- XMWVAUYSNFYWFN-UHFFFAOYSA-N 2-amino-4-bromo-n-[(2-fluoro-4-iodophenyl)methyl]benzamide Chemical compound NC1=CC(Br)=CC=C1C(=O)NCC1=CC=C(I)C=C1F XMWVAUYSNFYWFN-UHFFFAOYSA-N 0.000 description 1
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical class NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 description 1
- QMXVSYBJUXNLNL-UHFFFAOYSA-N 2-amino-n-[(2-fluoro-4-iodophenyl)methyl]-4-iodobenzamide Chemical compound NC1=CC(I)=CC=C1C(=O)NCC1=CC=C(I)C=C1F QMXVSYBJUXNLNL-UHFFFAOYSA-N 0.000 description 1
- IXMLVHZYRJDHDA-UHFFFAOYSA-N 2-amino-n-[(3,4-dichlorophenyl)methyl]benzenecarbothioamide Chemical compound NC1=CC=CC=C1C(=S)NCC1=CC=C(Cl)C(Cl)=C1 IXMLVHZYRJDHDA-UHFFFAOYSA-N 0.000 description 1
- LMXBWYRYHFCAHW-UHFFFAOYSA-N 2-amino-n-[(3,4-dichlorophenyl)methyl]benzenesulfonamide Chemical compound NC1=CC=CC=C1S(=O)(=O)NCC1=CC=C(Cl)C(Cl)=C1 LMXBWYRYHFCAHW-UHFFFAOYSA-N 0.000 description 1
- HKFLACQPLPQYQL-UHFFFAOYSA-N 2-amino-n-[(4-bromo-2-fluorophenyl)methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2C(=CC(Br)=CC=2)F)=C1N HKFLACQPLPQYQL-UHFFFAOYSA-N 0.000 description 1
- PFUTVJAUXICMDG-UHFFFAOYSA-N 2-amino-n-[(4-bromo-2-fluorophenyl)methyl]-4-fluorobenzamide Chemical compound NC1=CC(F)=CC=C1C(=O)NCC1=CC=C(Br)C=C1F PFUTVJAUXICMDG-UHFFFAOYSA-N 0.000 description 1
- RBGDLYUEXLWQBZ-UHFFFAOYSA-N 2-chlorobenzamide Chemical compound NC(=O)C1=CC=CC=C1Cl RBGDLYUEXLWQBZ-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- WPHUUIODWRNJLO-UHFFFAOYSA-N 2-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=CC=C1S(Cl)(=O)=O WPHUUIODWRNJLO-UHFFFAOYSA-N 0.000 description 1
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- MEENBKNFOGDXOL-UHFFFAOYSA-N 3-[(2-fluoro-4-iodophenyl)methyl]-7-iodo-1h-quinazoline-2,4-dione Chemical compound FC1=CC(I)=CC=C1CN1C(=O)C2=CC=C(I)C=C2NC1=O MEENBKNFOGDXOL-UHFFFAOYSA-N 0.000 description 1
- SZOXHZFAHOKCEP-UHFFFAOYSA-N 3-[(3,4-dichlorophenyl)methyl]-1h-quinazoline-2,4-dione Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1C(=O)C2=CC=CC=C2NC1=O SZOXHZFAHOKCEP-UHFFFAOYSA-N 0.000 description 1
- GUNKGGSUZIFUOG-UHFFFAOYSA-N 3-[(3,4-dichlorophenyl)methyl]-4-sulfanylidene-1h-quinazolin-2-one Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1C(=S)C2=CC=CC=C2NC1=O GUNKGGSUZIFUOG-UHFFFAOYSA-N 0.000 description 1
- FLZAIAYWNRAXHR-UHFFFAOYSA-N 3-[(4-bromo-2-fluorophenyl)methyl]-7-(trifluoromethyl)-1h-quinazoline-2,4-dione Chemical compound FC1=CC(Br)=CC=C1CN1C(=O)C2=CC=C(C(F)(F)F)C=C2NC1=O FLZAIAYWNRAXHR-UHFFFAOYSA-N 0.000 description 1
- ZRFLVZYXQZVYTF-UHFFFAOYSA-N 3-[(4-bromo-2-fluorophenyl)methyl]-7-fluoro-1h-quinazoline-2,4-dione Chemical compound C=1C(F)=CC=C(C2=O)C=1NC(=O)N2CC1=CC=C(Br)C=C1F ZRFLVZYXQZVYTF-UHFFFAOYSA-N 0.000 description 1
- QCDAQTIZNSSTSX-UHFFFAOYSA-N 3-[(4-bromo-2-fluorophenyl)methyl]-8-chloro-1h-quinazoline-2,4-dione Chemical compound FC1=CC(Br)=CC=C1CN1C(=O)C2=CC=CC(Cl)=C2NC1=O QCDAQTIZNSSTSX-UHFFFAOYSA-N 0.000 description 1
- KYCSZTJGIVSMEA-UHFFFAOYSA-N 3-[(4-bromo-2-fluorophenyl)methyl]-8-methoxy-1h-quinazoline-2,4-dione Chemical compound COC1=CC=CC(C2=O)=C1NC(=O)N2CC1=CC=C(Br)C=C1F KYCSZTJGIVSMEA-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ZEPFPIFGWCLYIN-UHFFFAOYSA-N 3-ethoxycarbonyl-2-methylbenzenesulfonic acid Chemical compound CCOC(=O)C1=C(C(=CC=C1)S(=O)(=O)O)C ZEPFPIFGWCLYIN-UHFFFAOYSA-N 0.000 description 1
- CGCVHJCZBIYRQC-UHFFFAOYSA-N 4,6-dichloro-1h-indole-2,3-dione Chemical compound ClC1=CC(Cl)=CC2=C1C(=O)C(=O)N2 CGCVHJCZBIYRQC-UHFFFAOYSA-N 0.000 description 1
- XOAKQCOPHMCADA-UHFFFAOYSA-N 4,8-dioxatricyclo[5.1.0.03,5]octane Chemical compound C1C2OC2CC2OC12 XOAKQCOPHMCADA-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
- ZIRHHEZLJGORGU-UHFFFAOYSA-N 4-bromo-2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C=C1[N+]([O-])=O ZIRHHEZLJGORGU-UHFFFAOYSA-N 0.000 description 1
- NTHPXJQLZIGPLM-UHFFFAOYSA-N 4-bromo-2-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC(Br)=CC=C1C(Cl)=O NTHPXJQLZIGPLM-UHFFFAOYSA-N 0.000 description 1
- WKOITHNBFAYKLW-UHFFFAOYSA-N 4-bromo-n-[(2-fluoro-4-iodophenyl)methyl]-2-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC(Br)=CC=C1C(=O)NCC1=CC=C(I)C=C1F WKOITHNBFAYKLW-UHFFFAOYSA-N 0.000 description 1
- FNYNMNKJWBOCPR-UHFFFAOYSA-N 4-bromo-n-[(4-bromo-2-fluorophenyl)methyl]-2-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC(Br)=CC=C1C(=O)NCC1=CC=C(Br)C=C1F FNYNMNKJWBOCPR-UHFFFAOYSA-N 0.000 description 1
- QWCJAHVNRQXIJE-UHFFFAOYSA-N 4-chloro-2-(phenylmethoxycarbonylamino)benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1NC(=O)OCC1=CC=CC=C1 QWCJAHVNRQXIJE-UHFFFAOYSA-N 0.000 description 1
- YTARMBZXIXCEEE-UHFFFAOYSA-N 4-chloro-n-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-2-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(Cl)C(C(F)(F)F)=C1 YTARMBZXIXCEEE-UHFFFAOYSA-N 0.000 description 1
- RHYGIQVXGKQWRK-UHFFFAOYSA-N 4-fluoro-n-[(2-fluoro-4-iodophenyl)methyl]-2-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC(F)=CC=C1C(=O)NCC1=CC=C(I)C=C1F RHYGIQVXGKQWRK-UHFFFAOYSA-N 0.000 description 1
- OVLVVBLYTQYCCS-UHFFFAOYSA-N 5-methyl-1h-quinazoline-2,4-dione Chemical compound N1C(=O)NC(=O)C2=C1C=CC=C2C OVLVVBLYTQYCCS-UHFFFAOYSA-N 0.000 description 1
- OAAGDVLVOKMRCQ-UHFFFAOYSA-N 5-piperidin-4-yl-3-pyridin-4-yl-1,2,4-oxadiazole Chemical compound C1CNCCC1C1=NC(C=2C=CN=CC=2)=NO1 OAAGDVLVOKMRCQ-UHFFFAOYSA-N 0.000 description 1
- OFKLPCYDGUKRKU-UHFFFAOYSA-N 7-chloro-3-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-1h-quinazoline-2,4-dione Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(CN2C(C3=CC=C(Cl)C=C3NC2=O)=O)=C1 OFKLPCYDGUKRKU-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 206010011026 Corneal lesion Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- LMBJWDJULPCUTN-UHFFFAOYSA-N O=S(C(C=C1)=CC=C1Cl)(O[S+]1C(C=C(C=C2)Cl)=C2N=C1)=O Chemical compound O=S(C(C=C1)=CC=C1Cl)(O[S+]1C(C=C(C=C2)Cl)=C2N=C1)=O LMBJWDJULPCUTN-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000003288 aldose reductase inhibitor Substances 0.000 description 1
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005910 alkyl carbonate group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical class C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940117975 chromium trioxide Drugs 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000006286 dichlorobenzyl group Chemical group 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002169 ethanolamines Chemical class 0.000 description 1
- JXSGGFMIAXFHSU-UHFFFAOYSA-N ethyl 2-(2,4-dioxoquinazolin-1-yl)acetate Chemical compound C1=CC=C2C(=O)NC(=O)N(CC(=O)OCC)C2=C1 JXSGGFMIAXFHSU-UHFFFAOYSA-N 0.000 description 1
- LIDDRPJGUCGVKD-UHFFFAOYSA-N ethyl 2-(2-carbamoyl-4,5-dichloroanilino)acetate Chemical compound CCOC(=O)CNC1=CC(Cl)=C(Cl)C=C1C(N)=O LIDDRPJGUCGVKD-UHFFFAOYSA-N 0.000 description 1
- IEMGWBMVQLVHEY-UHFFFAOYSA-N ethyl 2-(3-amino-6,7-dihydro-5h-cyclopenta[b]pyridin-7-yl)acetate Chemical compound NC1=CN=C2C(CC(=O)OCC)CCC2=C1 IEMGWBMVQLVHEY-UHFFFAOYSA-N 0.000 description 1
- IFPNMIQBDWEJEE-UHFFFAOYSA-N ethyl 2-(3-benzyl-4-oxo-2-sulfanylidenequinazolin-1-yl)acetate Chemical compound S=C1N(CC(=O)OCC)C2=CC=CC=C2C(=O)N1CC1=CC=CC=C1 IFPNMIQBDWEJEE-UHFFFAOYSA-N 0.000 description 1
- FWRGQSJWEUAZKD-UHFFFAOYSA-N ethyl 2-[2-(benzylcarbamoyl)anilino]acetate Chemical compound CCOC(=O)CNC1=CC=CC=C1C(=O)NCC1=CC=CC=C1 FWRGQSJWEUAZKD-UHFFFAOYSA-N 0.000 description 1
- YZTQFOPYJZJWPM-UHFFFAOYSA-N ethyl 2-[3-(3,4-dichlorophenyl)-2,4-dioxoquinazolin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C2=CC=CC=C2C(=O)N1C1=CC=C(Cl)C(Cl)=C1 YZTQFOPYJZJWPM-UHFFFAOYSA-N 0.000 description 1
- BXYIXOVQBKOXHD-UHFFFAOYSA-N ethyl 2-[3-(naphthalen-2-ylmethyl)-2,4-dioxoquinazolin-1-yl]acetate Chemical compound C1=CC=CC2=CC(CN3C(=O)C4=CC=CC=C4N(C3=O)CC(=O)OCC)=CC=C21 BXYIXOVQBKOXHD-UHFFFAOYSA-N 0.000 description 1
- HJECSYIYYIBAJP-UHFFFAOYSA-N ethyl 2-[3-[(3,4-dichlorophenyl)methyl]-2,4-bis(sulfanylidene)quinazolin-1-yl]acetate Chemical compound S=C1N(CC(=O)OCC)C2=CC=CC=C2C(=S)N1CC1=CC=C(Cl)C(Cl)=C1 HJECSYIYYIBAJP-UHFFFAOYSA-N 0.000 description 1
- YKEDZMUEYGWSDX-UHFFFAOYSA-N ethyl 2-[3-[(3,4-dichlorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C2=CC=CC=C2C(=O)N1CC1=CC=C(Cl)C(Cl)=C1 YKEDZMUEYGWSDX-UHFFFAOYSA-N 0.000 description 1
- ZZSNTSWAFJHDTG-UHFFFAOYSA-N ethyl 2-[3-[(4-bromo-2-fluorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C2=CC=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F ZZSNTSWAFJHDTG-UHFFFAOYSA-N 0.000 description 1
- XAAHMPHKJNTRKN-UHFFFAOYSA-N ethyl 2-[3-[(4-bromo-2-fluorophenyl)methyl]-6,7-dichloro-2,4-dioxoquinazolin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C2=CC(Cl)=C(Cl)C=C2C(=O)N1CC1=CC=C(Br)C=C1F XAAHMPHKJNTRKN-UHFFFAOYSA-N 0.000 description 1
- UHVCHPABYVWSQY-UHFFFAOYSA-N ethyl 2-[7-bromo-3-[(2-fluoro-4-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C2=CC(Br)=CC=C2C(=O)N1CC1=CC=C(I)C=C1F UHVCHPABYVWSQY-UHFFFAOYSA-N 0.000 description 1
- FKWQISKKVCKZQK-UHFFFAOYSA-N ethyl 2-[7-bromo-3-[(4-bromo-2-fluorophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C2=CC(Br)=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F FKWQISKKVCKZQK-UHFFFAOYSA-N 0.000 description 1
- XHIVILJVQFGULT-UHFFFAOYSA-N ethyl 2-[7-chloro-3-[(2-fluoro-4-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(I)C=C1F XHIVILJVQFGULT-UHFFFAOYSA-N 0.000 description 1
- VCTKRJKBGCACGX-UHFFFAOYSA-N ethyl 2-[7-chloro-3-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-2,4-dioxoquinazolin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(Cl)C(C(F)(F)F)=C1 VCTKRJKBGCACGX-UHFFFAOYSA-N 0.000 description 1
- XXNJVQDXMGMKQQ-UHFFFAOYSA-N ethyl 2-[7-fluoro-3-[(2-fluoro-4-iodophenyl)methyl]-2,4-dioxoquinazolin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)C2=CC(F)=CC=C2C(=O)N1CC1=CC=C(I)C=C1F XXNJVQDXMGMKQQ-UHFFFAOYSA-N 0.000 description 1
- VHUMPXOBXNPIQS-UHFFFAOYSA-N ethyl 2-benzylsulfonyloxyacetate Chemical compound CCOC(=O)COS(=O)(=O)CC1=CC=CC=C1 VHUMPXOBXNPIQS-UHFFFAOYSA-N 0.000 description 1
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 1
- LONGCUIECIAYIP-UHFFFAOYSA-N ethyl 2-methylsulfonyloxypropanoate Chemical compound CCOC(=O)C(C)OS(C)(=O)=O LONGCUIECIAYIP-UHFFFAOYSA-N 0.000 description 1
- FQTIYMRSUOADDK-UHFFFAOYSA-N ethyl 3-bromopropanoate Chemical compound CCOC(=O)CCBr FQTIYMRSUOADDK-UHFFFAOYSA-N 0.000 description 1
- ZCLGVXACCAZJOX-UHFFFAOYSA-N ethyl 3-chloropropanoate Chemical compound CCOC(=O)CCCl ZCLGVXACCAZJOX-UHFFFAOYSA-N 0.000 description 1
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000010575 fractional recrystallization Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- INHCSSUBVCNVSK-UHFFFAOYSA-L lithium sulfate Inorganic materials [Li+].[Li+].[O-]S([O-])(=O)=O INHCSSUBVCNVSK-UHFFFAOYSA-L 0.000 description 1
- MJTGQALMWUUPQM-UHFFFAOYSA-N m-Chlorobenzamide Chemical compound NC(=O)C1=CC=CC(Cl)=C1 MJTGQALMWUUPQM-UHFFFAOYSA-N 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- FLNDWHKVRHPOFO-UHFFFAOYSA-N n-[(2-fluoro-4-iodophenyl)methyl]-4-iodo-2-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC(I)=CC=C1C(=O)NCC1=CC=C(I)C=C1F FLNDWHKVRHPOFO-UHFFFAOYSA-N 0.000 description 1
- VFXWDLRVGAUBMA-UHFFFAOYSA-N n-[(4-bromo-2-fluorophenyl)methyl]-3-chloro-2-nitrobenzamide Chemical compound [O-][N+](=O)C1=C(Cl)C=CC=C1C(=O)NCC1=CC=C(Br)C=C1F VFXWDLRVGAUBMA-UHFFFAOYSA-N 0.000 description 1
- HEMQSPSFPNMJCY-UHFFFAOYSA-N n-[(4-bromo-2-fluorophenyl)methyl]-3-methoxy-2-nitrobenzamide Chemical compound COC1=CC=CC(C(=O)NCC=2C(=CC(Br)=CC=2)F)=C1[N+]([O-])=O HEMQSPSFPNMJCY-UHFFFAOYSA-N 0.000 description 1
- OJYXTHNXUULAIL-UHFFFAOYSA-N n-[(4-bromo-2-fluorophenyl)methyl]-4-chloro-2-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC(Cl)=CC=C1C(=O)NCC1=CC=C(Br)C=C1F OJYXTHNXUULAIL-UHFFFAOYSA-N 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- FKRCODPIKNYEAC-UHFFFAOYSA-N propionic acid ethyl ester Natural products CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 1
- ISYUCUGTDNJIHV-UHFFFAOYSA-N propyl 2-bromoacetate Chemical compound CCCOC(=O)CBr ISYUCUGTDNJIHV-UHFFFAOYSA-N 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229910052705 radium Inorganic materials 0.000 description 1
- HCWPIIXVSYCSAN-UHFFFAOYSA-N radium atom Chemical compound [Ra] HCWPIIXVSYCSAN-UHFFFAOYSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- KUYMVWXKHQSIAS-UHFFFAOYSA-N tert-butyl 2-chloroacetate Chemical compound CC(C)(C)OC(=O)CCl KUYMVWXKHQSIAS-UHFFFAOYSA-N 0.000 description 1
- RBTVSNLYYIMMKS-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)N1CC(N)C1 RBTVSNLYYIMMKS-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
- C07D239/96—Two oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/15—Six-membered rings
- C07D285/16—Thiadiazines; Hydrogenated thiadiazines
- C07D285/18—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines
- C07D285/20—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems
- C07D285/22—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D285/24—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Ophthalmology & Optometry (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Reproductive Health (AREA)
- Neurosurgery (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB858524663A GB8524663D0 (en) | 1985-10-07 | 1985-10-07 | Quinazoline derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HUT41747A HUT41747A (en) | 1987-05-28 |
| HU196972B true HU196972B (en) | 1989-02-28 |
Family
ID=10586291
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU864192A HU196972B (en) | 1985-10-07 | 1986-10-06 | Process for producing new quinazoline derivatives and pharmaceutical compositions containing them as active components |
Country Status (23)
| Country | Link |
|---|---|
| US (2) | US4734419A (OSRAM) |
| EP (1) | EP0218999B1 (OSRAM) |
| JP (3) | JPS6296476A (OSRAM) |
| KR (1) | KR940007270B1 (OSRAM) |
| CN (1) | CN1017242B (OSRAM) |
| AT (1) | ATE60761T1 (OSRAM) |
| AU (1) | AU596611B2 (OSRAM) |
| CA (1) | CA1289139C (OSRAM) |
| DE (1) | DE3677452D1 (OSRAM) |
| DK (1) | DK158838C (OSRAM) |
| ES (1) | ES2021266B3 (OSRAM) |
| FI (1) | FI90234C (OSRAM) |
| GB (1) | GB8524663D0 (OSRAM) |
| GR (1) | GR3001502T3 (OSRAM) |
| HK (1) | HK6993A (OSRAM) |
| HU (1) | HU196972B (OSRAM) |
| IE (1) | IE59309B1 (OSRAM) |
| IL (1) | IL80213A (OSRAM) |
| NO (1) | NO171785C (OSRAM) |
| SG (1) | SG112092G (OSRAM) |
| SU (1) | SU1588283A3 (OSRAM) |
| UA (1) | UA5562A1 (OSRAM) |
| ZA (1) | ZA867043B (OSRAM) |
Families Citing this family (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8524663D0 (en) * | 1985-10-07 | 1985-11-13 | Fujisawa Pharmaceutical Co | Quinazoline derivatives |
| PH23853A (en) * | 1986-08-21 | 1989-11-23 | Pfizer | Pyridopyrimidinediones |
| US4889851A (en) * | 1986-11-21 | 1989-12-26 | Fujisawa Pharmaceutical Co, Ltd. | Benzothiadiazine compounds, and pharmaceutical composition comprising the same |
| US4931440A (en) * | 1987-07-29 | 1990-06-05 | Fujisawa Pharmaceutical Company, Ltd. | Uricosuric composition |
| AU599515B2 (en) * | 1987-09-16 | 1990-07-19 | Taiho Pharmaceutical Co., Ltd. | Thienopyrimidine derivatives |
| JP2621460B2 (ja) * | 1988-02-29 | 1997-06-18 | 藤沢薬品工業株式会社 | 利尿または降圧剤 |
| US5324747A (en) * | 1992-07-15 | 1994-06-28 | Hoffmann-La Roche Inc. | N-substituted anilines, inhibitors of phospholipases A2 |
| NZ254550A (en) * | 1992-09-28 | 1997-08-22 | Pfizer | Use of nitrogen-substituted pyrimidines to prepare medicaments useful for treatment or prevention of diabetic complications |
| EP0847382B1 (de) * | 1995-08-31 | 2000-12-20 | Clariant GmbH | Monoester der carboxymethylenanthranilsäuren und verfahren zu ihrer herstellung |
| DE19532052C2 (de) * | 1995-08-31 | 1998-11-19 | Clariant Gmbh | Verfahren zur Herstellung von Chinazolinderivaten |
| EP0781767B1 (en) * | 1995-12-26 | 2001-09-05 | Sumitomo Chemical Company, Limited | Process for producing isatoic anhydrides |
| WO1997024335A1 (en) * | 1995-12-28 | 1997-07-10 | Fuji Chemical Industry Co., Ltd. | Process for the preparation of 3-dihalobenzyl-2,4-quinazolinedione derivatives |
| DE69701647T2 (de) * | 1996-02-01 | 2000-09-07 | Sumitomo Chemical Co., Ltd. | Verfahren zur Herstellung von Dioxochinazolinen |
| DE19650975A1 (de) * | 1996-12-09 | 1998-06-10 | Basf Ag | Neue heterocyclisch substituierte Benzamide und deren Anwendung |
| DE69836321T2 (de) * | 1997-04-15 | 2007-06-28 | Csir, Pretoria | Pflanzenextrakte mit appetitzügelnder Aktivität |
| US6444816B1 (en) | 1997-10-27 | 2002-09-03 | Dr. Reddy's Research Foundation | Fused 7-oxo-pyrimidinyl compounds, preparation, composition and use thereof |
| WO1999038497A2 (en) | 1998-01-30 | 1999-08-05 | R-Tech Ueno, Ltd. | Ophthalmic composition |
| AU2129500A (en) * | 1999-01-25 | 2000-08-07 | Fujisawa Pharmaceutical Co., Ltd. | Eye drops |
| JP2003516309A (ja) * | 1999-02-18 | 2003-05-13 | 株式会社アールテック・ウエノ | 涙液分泌障害を除く外分泌障害処置剤 |
| KR20020011966A (ko) * | 1999-03-09 | 2002-02-09 | 후지야마 아키라 | 퀴나졸린 유도체 또는 그의 염의 제조법 |
| US6545004B1 (en) | 1999-10-27 | 2003-04-08 | Cytokinetics, Inc. | Methods and compositions utilizing quinazolinones |
| GB2396815B (en) * | 1999-10-27 | 2004-09-08 | Phytopharm Plc | A composition comprising a pregnenone derivative and an NSAID |
| US7230000B1 (en) | 1999-10-27 | 2007-06-12 | Cytokinetics, Incorporated | Methods and compositions utilizing quinazolinones |
| US6380200B1 (en) | 1999-12-07 | 2002-04-30 | Pfizer, Inc. | Combination of aldose reductase inhibitors and selective serotonin reuptake inhibitors for the treatment of diabetic complications |
| GB2363985B (en) * | 2000-06-30 | 2004-09-29 | Phytopharm Plc | Extracts,compounds & pharmaceutical compositions having anti-diabetic activity and their use |
| EP1337272A2 (en) | 2000-11-30 | 2003-08-27 | Pfizer Products Inc. | Combination of gaba agonists and aldose reductase inhibitors |
| WO2002098462A1 (en) * | 2001-06-01 | 2002-12-12 | Ono Pharmaceutical Co., Ltd. | Remedies containing aldose reductase inhibitor as the active ingredient for demyelinating diseases or diseases associated with demyelination |
| WO2003070701A2 (en) * | 2002-02-15 | 2003-08-28 | Cytokinetics, Inc. | Syntheses of quinazolinones |
| EP2316469A1 (en) | 2002-02-22 | 2011-05-04 | Shire LLC | Delivery system and methods for protecting and administering dextroamphetamine |
| BR0309892A2 (pt) * | 2002-05-09 | 2011-04-05 | Cytokinetics Inc | composto, composição, métodos para modular a atividade da cinesina de ksp, para inibir a ksp, e para o tratamento de uma doença proliferativa celular, e, uso de um composto |
| AU2003270015A1 (en) * | 2002-05-09 | 2003-12-02 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| WO2004026226A2 (en) * | 2002-05-10 | 2004-04-01 | Cytokinetics, Inc. | Compounds, compositions and methods |
| US7038048B2 (en) * | 2002-05-23 | 2006-05-02 | Cytokinetics, Inc. | 3H-pyridopyrimidin-4-one compounds, compositions, and methods of their use |
| US7041676B2 (en) * | 2002-06-14 | 2006-05-09 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| EP1537089A4 (en) * | 2002-07-23 | 2008-04-16 | Cytokinetics Inc | CONNECTIONS, COMPOSITIONS AND PROCEDURES |
| EP1539180A4 (en) * | 2002-08-21 | 2006-08-30 | Cytokinetics Inc | COMPOUNDS, COMPOSITIONS AND METHODS |
| JP2006501306A (ja) * | 2002-09-30 | 2006-01-12 | サイトキネティクス・インコーポレーテッド | 化合物、組成物および方法 |
| JP2007510652A (ja) * | 2003-11-03 | 2007-04-26 | サイトキネティクス・インコーポレーテッド | ピリミジン−４−オン化合物、組成物、および方法 |
| US20050148593A1 (en) * | 2003-11-07 | 2005-07-07 | Gustave Bergnes | Compounds, compositions, and methods |
| JP2007513154A (ja) * | 2003-12-08 | 2007-05-24 | サイトキネティクス・インコーポレーテッド | 化合物、組成物及び方法 |
| US20070010537A1 (en) * | 2004-08-20 | 2007-01-11 | Kazumasa Hamamura | Fused pyramidine derivative and use thereof |
| US20110092566A1 (en) * | 2004-11-19 | 2011-04-21 | Srivastava Satish K | Treatment of cancer with aldose reductase inhibitors |
| ES2525152T3 (es) * | 2006-07-19 | 2014-12-18 | E.I. Du Pont De Nemours And Company | Proceso de obtención de 2-amino-5-halobenzamidas 3-sustituidas |
| CN101765433A (zh) | 2007-03-12 | 2010-06-30 | Zadec私人有限责任公司 | 一种抗糖尿病的红灌木提取物 |
| CA2685202C (en) | 2007-03-23 | 2017-11-28 | The Board Of Regents Of The University Of Texas System | Methods for treating allergic asthma |
| AU2008285795A1 (en) * | 2007-08-03 | 2009-02-12 | F. Hoffmann-La Roche Ag | Pyridinecarboxamide and benzamide derivatives as TAAR1 ligands |
| US20090270490A1 (en) * | 2008-04-24 | 2009-10-29 | The Board Of Regents Of The University Of Texas System | Methods involving aldose reductase inhibition |
| CN102219759B (zh) * | 2010-04-16 | 2013-07-24 | 中国科学院上海药物研究所 | 芳基甲酰胺类化合物及其制备方法、药物组合物和用途 |
| CA2822672C (en) | 2010-12-23 | 2018-06-05 | The Board Of Regents Of The University Of Texas System | Methods for treating copd |
| BR112015028152A2 (pt) | 2013-05-10 | 2017-07-25 | Nimbus Apollo Inc | inibidores de acc e usos dos mesmos |
| BR112015028171A8 (pt) | 2013-05-10 | 2017-08-22 | Nimbus Apollo Inc | Inibidores de acc e seu uso |
| HK1221420A1 (zh) | 2013-05-10 | 2017-06-02 | Gilead Apollo, Inc. | Acc抑制剂和其用途 |
| TW201623257A (zh) | 2014-05-09 | 2016-07-01 | 奧利安公司 | 藥理活性之喹唑啉二酮衍生物 |
| WO2019165195A1 (en) | 2018-02-22 | 2019-08-29 | Srivastava Satish | Combination therapy for the treatment of cancer |
| CN111499616B (zh) * | 2020-05-07 | 2022-07-22 | 盐城工学院 | 一种芳杂环取代的喹唑啉酮衍生物及其合成方法与应用 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1491510A (en) * | 1973-12-14 | 1977-11-09 | Hisamitsu Pharmaceutical Co | 1-nitrophenylquinazoline-2,4(1h,3h)-diones |
| DE2652144A1 (de) * | 1976-11-16 | 1978-05-18 | Merck Patent Gmbh | Neue chinazolindione |
| CA1161036A (en) * | 1980-05-15 | 1984-01-24 | Masayuki Ishikawa | Quinazoline-dione compounds, process for production thereof and pharmaceutical use thereof |
| DE3172006D1 (en) * | 1980-05-22 | 1985-10-03 | Masayuki Ishikawa | Novel quinazoline-dione compounds, process for production thereof and pharmaceutical use thereof |
| JPS58159480A (ja) * | 1982-03-17 | 1983-09-21 | Chugai Pharmaceut Co Ltd | 新規なフエニルピペラジン誘導体 |
| DD232702A1 (de) * | 1982-09-20 | 1986-02-05 | Adw Ddr | Verfahren zur herstellung von 1,2,3,4-tetrahydrochinazolin-2,4-dion-essigsaeuren, deren salzen und estern |
| US4490374A (en) * | 1982-09-30 | 1984-12-25 | Ortho Pharmaceutical Corporation | 5,6-Dialkoxy-3,4-optionally substituted-2(1H)quinazolinones, composition and method of use |
| JPS59186963A (ja) * | 1983-04-08 | 1984-10-23 | Chugai Pharmaceut Co Ltd | 新規なフエニルピペラジン誘導体 |
| GB8524663D0 (en) * | 1985-10-07 | 1985-11-13 | Fujisawa Pharmaceutical Co | Quinazoline derivatives |
-
1985
- 1985-10-07 GB GB858524663A patent/GB8524663D0/en active Pending
-
1986
- 1986-09-16 ZA ZA867043A patent/ZA867043B/xx unknown
- 1986-09-16 US US06/908,005 patent/US4734419A/en not_active Expired - Lifetime
- 1986-09-23 IE IE252086A patent/IE59309B1/en not_active IP Right Cessation
- 1986-09-25 DK DK459086A patent/DK158838C/da not_active IP Right Cessation
- 1986-09-29 FI FI863917A patent/FI90234C/fi not_active IP Right Cessation
- 1986-10-02 ES ES86113559T patent/ES2021266B3/es not_active Expired - Lifetime
- 1986-10-02 AT AT86113559T patent/ATE60761T1/de not_active IP Right Cessation
- 1986-10-02 IL IL80213A patent/IL80213A/xx not_active IP Right Cessation
- 1986-10-02 DE DE8686113559T patent/DE3677452D1/de not_active Expired - Fee Related
- 1986-10-02 EP EP86113559A patent/EP0218999B1/en not_active Expired - Lifetime
- 1986-10-03 SU SU864028362A patent/SU1588283A3/ru active
- 1986-10-03 UA UA4028362A patent/UA5562A1/uk unknown
- 1986-10-03 CA CA000519759A patent/CA1289139C/en not_active Expired - Fee Related
- 1986-10-06 AU AU63589/86A patent/AU596611B2/en not_active Ceased
- 1986-10-06 NO NO863980A patent/NO171785C/no not_active IP Right Cessation
- 1986-10-06 HU HU864192A patent/HU196972B/hu not_active IP Right Cessation
- 1986-10-06 JP JP61237605A patent/JPS6296476A/ja active Granted
- 1986-10-07 KR KR86008374A patent/KR940007270B1/ko not_active Expired - Fee Related
- 1986-10-07 CN CN86106984A patent/CN1017242B/zh not_active Expired
-
1987
- 1987-12-08 US US07/130,297 patent/US4883800A/en not_active Expired - Lifetime
-
1988
- 1988-08-22 JP JP63207571A patent/JPH01125322A/ja active Granted
- 1988-08-22 JP JP63207570A patent/JPH0794447B2/ja not_active Expired - Lifetime
-
1991
- 1991-02-25 GR GR90401160T patent/GR3001502T3/el unknown
-
1992
- 1992-10-27 SG SG1120/92A patent/SG112092G/en unknown
-
1993
- 1993-01-28 HK HK69/93A patent/HK6993A/en not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HU196972B (en) | Process for producing new quinazoline derivatives and pharmaceutical compositions containing them as active components | |
| JP3081172B2 (ja) | 含窒素複素環化合物 | |
| US4818756A (en) | 2-pyrimidinyl-1-piperazine derivatives, processes for their preparation and medicaments containing them | |
| KR100622323B1 (ko) | 질소-함유헤테로고리화합물 | |
| EP0637300B1 (en) | Antiproliferative quinazolines | |
| JP2896532B2 (ja) | 新規なピリミジン誘導体およびその製造方法 | |
| US20100016354A1 (en) | Novel oxadiazole derivatives and thiadiazole derivatives having neovascularization inhibitory activity | |
| HU207999B (en) | Process for producing quinazolin-3-alkanoic acids and pharmaceutical compositions containing them | |
| WO1999014203A1 (en) | Nitrogenous fused-ring compounds, process for the preparation of the same, and drugs | |
| US20050245548A1 (en) | Alkynylated fused ring pyrimidine compounds | |
| US4782055A (en) | Imidazopyridine compounds useful in the treatment of ulcers | |
| CZ20031334A3 (cs) | Isochinolinové deriváty a jejich použití jako inhibitory | |
| US4889851A (en) | Benzothiadiazine compounds, and pharmaceutical composition comprising the same | |
| US5574039A (en) | Antiproliferative compounds having nitrogen-containing tricyclic ring systems and phenyl substituents | |
| JPH07242666A (ja) | 複素環化合物 | |
| US4608375A (en) | Quinazolinone derivatives, processes for the preparation thereof and pharmaceutical composition comprising the same | |
| JPH11152275A (ja) | 含窒素縮合環化合物、その製造法および剤 | |
| US5187276A (en) | 2-pyrimidinyl-1-piperazine derivatives | |
| US3974161A (en) | Fused pyrimidin-4(3H)-ones as antiallergy agents | |
| JPH01157955A (ja) | 新規複素環誘導体およびその製造法 | |
| KR100282153B1 (ko) | 3-알킬피롤록3,2-씨퀴놀린유도체 | |
| WO1998045298A1 (en) | Antiviral agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HU90 | Patent valid on 900628 | ||
| HMM4 | Cancellation of final prot. due to non-payment of fee | ||
| HMM4 | Cancellation of final prot. due to non-payment of fee | ||
| HMM4 | Cancellation of final prot. due to non-payment of fee |